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Could local immune reaction in the gut be a cause of IBS pain?

By Apollo 24/7, Published on - 29 April 2021

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A chronic gastrointestinal disorder known as Irritable bowel syndrome (IBS) affects the large intestine. It is called a functional disorder as it is not linked to any structural or biochemical abnormalities on examination. IBS is a symptom-based condition that is not known to cause damage to the gastrointestinal tract. The hallmark symptom of IBS is abdominal pain or discomfort shortly after eating. The abdominal pain is associated with changes in bowel movement causing constipation and/or diarrhoea. These symptoms are attributed to factors such as diet, emotional stress, or an infection. Recent research suggests that the pain caused by infection-induced IBS may be because of a local immune reaction to food in the intestine.

Food allergy and IBS

It is well known that food is a common trigger for IBS. It is believed that many people with IBS are allergic to specific foods. The food allergy tests rely on the presence of allergy-related antibodies known as immunoglobulin E (IgE) molecules in the blood. But according to studies at the University of Nottingham, blood samples of people with IBS symptoms that are thought to be triggered by food showed no evidence of IgE antibodies. However, recent research studies show a novel concept of allergic reaction in IBS that is localized to the gut.

Role of immune cells in IBS

In the past, studies at the University of Bologna show that the immune system in people with IBS is different. The biopsies of intestinal tissue from these people showed activated mast cells. Mast cells are immune cells that are activated in response to infections. The mast cells release chemicals called histamines that mediate local inflammatory responses such as hypersensitivity and allergic reactions. But the mast cell activation was found in IBS patients with no active infection. It was also seen that the mast cells were found in the vicinity of nerve cells in the gut and the chemicals released made these neurons hypersensitive and fire excessively.

Intestinal infection and IBS pain

Researchers at the KU Leuven university studied intestinal infections as they are the most common and well-known cause of IBS. They found that in about 10% of people, symptoms of IBS were seen after complete recovery from an intestinal infection. Studies suggested that low-grade inflammation that remained in the intestine caused the IBS pain. But to the team’s surprise, intestinal biopsies of these people did not show inflammation.

Altered gut reactions to foods

The researchers hypothesized that the intestinal infection could alter the reaction of the intestine to protein fragments in foods known as antigens. While fighting an infection, the immune system becomes hypersensitive and may mistakenly identify food antigens as foreign molecules. This response to food antigens that may persist even after the infection subsides is said to be the cause of IBS pain and cramping that is experienced after a meal.

The team further studied the hypothesis by experiments in mice. They infected the mice with harmful intestinal bacteria and simultaneously fed them antigens from egg whites. After the mice recovered from the infection, they again fed them with antigens. These mice developed abdominal pain associated with muscle contractions. Additionally, the mice that were not fed the egg white protein while they were infected, had no symptoms of abdominal pain.

Local immune reactions in the intestine

Researchers found that following an infection, the egg white proteins (antigens) were shown to bind to IgE antibodies on the mast cells causing their activation and histamine release. The researchers observed the mice for four weeks and found that the reaction to egg protein continued. The study also emphasized the connection between mast cells and the hyperactivity of nearby gut neurons that was hypothesized in earlier research. They inferred that hypersensitivity and over-activity of neurons are interpreted as pain associated with IBS.

They said that the observation in mice is not a food allergy because it is a local immune reaction of mast cell activation in the gut. In people allergic to peanuts or cow’s milk, IgE antibodies that are produced circulate in the blood, causing the symptoms of allergic reaction all over the body. However, the blood samples of mice did not show IgE antibodies indicating that it is not an egg white allergy.

To confirm these local reactions in people with IBS, studies were conducted with common allergy-inducing foods. The results obtained were negative. However, when the researchers injected these allergens rectally, all of them showed a local IgE reaction in the gut to at least one of the antigens in the subsequent tests. The same tests were carried out on healthy people, and a small percentage of them showed a mild reaction. But the researchers suspect that these people did not show any symptoms as their intestines could probably tolerate mild reactions.

Conclusion

The research study shows that the pain associated with IBS is due to a local intestinal reaction in the case of infection-induced IBS. Further research is required to see if these reactions are specific to certain foods and also whether these immune reactions occur only in case of infections or with other triggers such as stress. However, the research gives scope for immune-based therapy for IBS as these are local reactions involving mast cells and IgE molecules.

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